Primary hyperaldosteronism occurs when there are excessive levels of aldosterone independent of the renin-angiotensin axis. Secondary hyperaldosteronism occurs due to high renin levels.
The causes of primary hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome) – the most common cause of hyperaldosteronism (,80% of all cases). These are usually unilateral and solitary and are more common in women.
Adrenal hyperplasia – this accounts for ,15% of all cases. Usually, bilateral adrenal hyperplasia (BAH) but can be unilateral rarely. More common in men than women.
Adrenal cancer – a rare diagnosis but essential not to miss
Familial aldosteronism – a rare group of inherited conditions affecting the adrenal glands
The causes of secondary hyperaldosteronism include:
Drugs – diuretics
Obstructive renal artery disease – renal artery stenosis and atheroma
Renal vasoconstriction – occurs in accelerated hypertension
Oedematous disorders – heart failure, cirrhosis and nephrotic syndrome
Patients are often asymptomatic. When clinical features are present, the classically described presentation of hyperaldosteronism is with:
Hypertension
Hypokalaemia
Metabolic alkalosis
Sodium levels can be normal or slightly raised
Other, less common, clinical features include:
Lethargy
Headaches
Muscle weakness (from persistent hypokalaemia)
Polyuria and polydipsia
Intermittent paraesthesia
Tetany and paralysis (rare)
Often the earliest sign of hyperaldosteronism is from aberrant urea and electrolytes showing hypokalaemia and mild hypernatraemia. If the patient is taking diuretics, and the diagnosis is suspected, these should be repeated after the patient has taken off diuretics.
If the diagnosis is suspected, plasma renin and aldosterone levels should be checked. Low renin and high aldosterone levels (with a raised aldosterone: renin ratio) is suggestive of primary aldosteronism.
If the renin: aldosterone ratio is high, then the effect of posture on renin, aldosterone and cortisol can be investigated to provide further information about the underlying cause of primary hyperaldosteronism. Levels should be measured lying at 9 am and standing at noon:
If aldosterone and cortisol levels fall on standing, this is suggestive of an ACTH dependent cause, e.g. adrenal adenoma (Conn’s syndrome)
If aldosterone levels rise and cortisol levels fall on standing, this is suggestive of an angiotensin-II dependent cause, e.g. BAH
Other investigations that can help to distinguish between an adrenal adenoma and adrenal hyperplasia include:
CT scan
MRI scan
Selective adrenal venous sampling

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

All nephrons have their renal corpuscles in the renal cortex. Cortical nephrons have their renal corpuscles in the outer part of the cortex and relatively short loops of Henle. Juxtamedullary nephrons have their corpuscles in the inner third of the cortex, close to the corticomedullary junction, with long loops of Henle extending into the renal medulla.

Forceful expiration is primarily produced by the deeper thoracic muscles (internal and innermost intercostal muscles, subcostals and transversus thoracis) aided by contraction of the abdominal wall muscles which increase intra-abdominal pressure thus further reducing the volume of the thorax.

Abciximab, eptifibatide and tirofiban are GPIIb/IIIa inhibitors, inhibiting platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive molecules.

Cephalosporins of the first generation  include cephalexin, cefradine, and cefadroxil. Urinary tract infections, respiratory tract infections, otitis media, and skin and soft-tissue infections are all treated with them.

Second-generation cephalosporins include cefuroxime, cefaclor, and cefoxitin. These cephalosporins are less vulnerable to beta-lactamase inactivation than the ‘first-generation’ cephalosporins. As a result, they’re effective against germs that are resistant to other antibiotics, and they’re especially effective against Haemophilus influenzae.

Cephalosporins of the third generation include cefotaxime, ceftazidime, and ceftriaxone. They are more effective against Gram-negative bacteria than second generation’ cephalosporins. They are, however, less effective against Gram-positive bacteria such Staphylococcus aureus than second-generation cephalosporins.

Approximately 65 – 70% of filtered K+is reabsorbed in the proximal tubule. Potassium reabsorption is tightly linked to that of sodium and water. The reabsorption of sodium drives that of water, which may carry some potassium with it. The potassium gradient resulting from the reabsorption of water from the tubular lumen drives the paracellular reabsorption of potassium and may be enhanced by the removal of potassium from the paracellular space via the Na+/K+ATPase pump. In the later proximal tubule, the positive potential in the lumen also drives the potassium reabsorption through the paracellular route.

Myofibrils, which are around 1 m in diameter, make up each myofiber. The cytoplasm separates them and arranges them in a parallel pattern along the cell’s long axis. These myofibrils are made up of actin and myosin filaments that are repeated in sarcomeres, which are the myofiber’s basic functional units.

Myofilaments are the filaments that make up myofibrils, and they’re made mostly of proteins. Myofilaments are divided into three categories:

Myosin filaments are thick filaments made up mostly of the protein myosin.
Actin filaments are thin filaments made up mostly of the protein actin.
Elastic filaments are mostly made up of the protein titin.
The sarcomere is a Z-line segment that connects two adjacent Z-lines.
The I-bands are thin filament zones that run from either side of the Z-lines to the thick filament’s beginning.
Between the I-bands is the A-band, which spans the length of a single thick filament.
The H-zone is a zone of thick filaments that is not overlaid by thin filaments in the sarcomere’s centre. The H-zone keeps the myosin filaments in place by surrounding them with six actin filaments each.
The M-band (or M-line) is a disc of cross-connecting cytoskeleton elements in the centre of the H-zone.
The thick filament is primarily made up of myosin. The thin filament is primarily made up of actin. Actin, tropomyosin, and troponin are found in a 7:1:1 ratio in thin filaments.

Approximately half of total serum calcium is in the free or ionised Ca2+ state, 40% is attached to plasma proteins (mostly albumin), and the remaining 10% is in complexes with organic ions like citrate and phosphate. The ionized form is the only one that works.

Hypothyroidism occurs when there is a deficiency of circulating thyroid hormones. It is commoner in women and is most frequently seen in the age over 60.

Iodine deficiency is the commonest cause of hypothyroidism worldwide.

In developed countries, iodine deficiency is not a problem and autoimmune thyroiditis is the commonest cause.